Registration Dossier

Administrative data

Description of key information

The substance caused transient, slight irritation of the rabbit skin evidenced as very slight to well-defined erythema and very slight edema. Erythema was fully reversible in all animals within 72 hours following the commencement of exposure. Edema (very slight) seen in only 2 animals was fully reversible within 72 hours after the start of exposure. The test substance caused no irritating effects on the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(48 hour scoring not performed, 10/14 hour dark/light rhythm, treatment on intact and abraded skin, occlusive treatment, 24 hour long treatment)
Principles of method if other than guideline:
Draize test
GLP compliance:
no
Species:
rabbit
Strain:
other: Russian breed
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Weight at study initiation: 1.5 - 2 kg
- Housing: individually in metal cages
- Diet: ad libitum; standard rabbit food (NAFAG Gossau SG)
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10/14
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated parts of the same rabbit
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g
Duration of treatment / exposure:
24 hours
Observation period:
Scoring of skin irritation was performed 24 and 72 hours after initiation of treatment. Animals were observed until the reversal of irritation effects.
Number of animals:
6
Details on study design:
TEST SITE
- Two days before treatment the entire back, and the flank of the rabbits were shaved and immediately before treatment, the shaven skin of the left side was slightly scarified. The right side was not scarified.
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: The patches were covered with an impermeable material and fastened with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: no
- Time after start of exposure: 24 hours

SCORING SYSTEM: draize system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 and 72 hours after start of treatment
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours after start of treatment
Remarks on result:
other: 48h not investigated
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 and 72 hours after start of treatment
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours after start of treatment
Remarks on result:
other: 48h not investigated
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24 and 72 hours after start of treatment
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours after start of treatment
Remarks on result:
other: 48h not investigated
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24 and 72 hours after start of treatment
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 48h not investigated
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24 and 72 hours after start of treatment
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours after start of treatment
Remarks on result:
other: 48h not investigated
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 24 and 72 hours after start of treatment
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours after start of treatment
Remarks on result:
other: 48h not investigated
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 and 72 hours after start of treatment
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours after start of treatment
Remarks on result:
other: 48h not investigated
Irritation parameter:
edema score
Basis:
animal: 2, 3, 4 and 6
Time point:
other: 24 and 72 hours after start of treatment
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 48h not investigated
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 24 and 72 hours after start of treatment
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours after start of treatment
Remarks on result:
other: 48h not investigated
Other effects:
Effects on scarified skin 24 hours after start of exposure (6 animals)
- Erythema: 2 (each of 5 animals), 1 (1 animal)
- Edema: 1 (each of 4 animals), 0 (2 animals)

Effects on scarified skin 72 hours after start of exposure (6 animal)
- Erythema: 1 (each of 4 animals), 0 (2 animals)
- Edema: 0 (all animals)

Only results of the non scarified skin sections are adopted in the final assessment for skin irritation.

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline standards with acceptable restrictions - Incomplete characterisation of test substance e.g. analytical purity of test article was not given in the report.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(10/14 hour dark/light rhythm, 6 test animals)
Principles of method if other than guideline:
Draize method
GLP compliance:
no
Species:
rabbit
Strain:
other: Russian breed
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no data
- Weight at study initiation: 1.5 - 2 kg
- Housing: individually in metal cages
- Diet: ad libitum; standard rabbit food (NAFAG Gossau SG)
- Water: ad libitum
- Acclimation period: 8 days. Only rabbits with normal opthalmic findings were used in the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10/14
Vehicle:
unchanged (no vehicle)
Controls:
other: other eye (not treated)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
Duration of treatment / exposure:
After instillation, eyes were not washed.
Observation period (in vivo):
Eye irritation was scored on day 1, 2, 3, 4, and 7.
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: yes (in 3 of 6 animals); with luke warm water
- Time after start of exposure: 30 sec after instillation

SCORING SYSTEM: draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(6 animals)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
(6 animals)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(6 animals)
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(6 animals)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Score for each animal and each measure parameters on day 4 and 7 after treatment = 0
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a primary dermal irritation study, performed using a method identical to that described in the Federal Register, 38, No.187 §1500.41, 0.5 g of the test substance (no data on analytical purity) was applied under occlusive cover to the intact and abraded skin (2.5 x 2.5 cm) of 6 rabbits of russian breed. Treatment was terminated (skins were not washed) 24 hours following application and the animals were observed until reversal of skin irritation symptoms. Irritation was scored according to the Draize method 24 and 72 hours after begin of treatment. Average scores per animal - computed from the individual scores on intact skin at the 24 and 72 hour post start of treatment - ranged from 0 - 1 for erythema (maximal attainable score = 4), and 0 – 0.5 for edema (maximal attainable score = 4). All effects were reversible within 72 hours after start of exposure. Because of its lack of scientific justification and gross deviation from today's acceptable standardized procedures for the appraisal of skin irritation, results from the abraded skins are not included in the final judgment for skin irritation of the test substance.

Eye irritation

The eye irritation potential of the test substance was determined in a procedure identical to the procedure described in the Federal Register 38, No.187 §1500.42. 0.1 g of the substance was applied to the conjunctival sac of the left eye of 6 rabbits each after which the eye lids were closed for one second. The right eye remained untreated and served as control. 30 sec. after instillation the treated eyes were rinsed with water in 3 of the 6 animals. Irritation was appraised after 24, 48, 72, 96 and 168 hours. Average draize scores after 24, 48 and 72 hours were calculated per animal for corneal opacity, iritis, conjunctivae redness and chemosis and used for assessment of irritation potential. No indication of eye irritation was seen: All scores for redness, corneal opacity, chemosis and iritis were zero in all animals.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification. Based on the criteria laid down in Regulation (EC) No.1272/2008, classification for skin and eye irritation is not warranted.